Addition product of a metal hydrocarbon mercaptide with an alpha-halogamma-butyrolactone



United States Patent ADDITION PRODUCT OF A METAL HYDROCAR- BON MERCAPTIDE WITH AN ALPHA-HALO- GAMMA-BUTYROLACTONE Arthur F. Wagner, Princeton, N. 3., assignor to Merck 59; 'Co., Inc., Rahway, N. ,L, a corporation of New ersey No Drawing. Original application December 30, 1954, Serial No. 478,920. Divided and this application April 25, 1956, Serial No. 580,461

6 Claims. (Cl. 260347.2)

found to have the structure and was giventhe common name: 6-thioctic acid, as is disclosed in the J. Am. Chem. Soc. 74, 3455 (1952). Although -:[3-(1,2:dithiacyclopentyl)l pentanoic acid can be isolated from natural materials such as liver, the .ditficulties encountered and low yields obtained have indicated the need for a practical synthetic method of producing the desired product.

Therefore, an object of this invention is to provide novel compounds useful for the synthetic production of 5-[3-(1,2-dithiacyclopentyl)] pentanoic acid. A further object is to provide processes for preparing these novel compounds.

According to one embodiment of the present invention novel o'Y-bisihydrocarbon substituted mercapto] butyric acids 'areprovided having the formula:

om-cm-on-o 0 OH SR SR wherein R is ahydrocarbon radical such as an alkyl, alkenyl, aryl or aralkyl group together with processes and intermediates useful for preparing the same. These compounds are useful in the synthesis of 5-[3-(1',2-dithiacyclopentyl)] pentanoic acid.

The novel a,'y-biS [hydrocarbon substituted mercapto] butyric acids are produced by reacting an wy-dihalobutyric acid with an ammonium, alkali metal or alkaline earth metal hydrocarbon mercaptide to form the corresponding ammonium, alkali metal or alkaline earth metal salt of the ayy-bislhydrocarbon substituted mercapto] butyric acidand subsequently hydrolyzing the salt to the corresponding raw-bis [hydrocarbon substituted mercapto] butyric acid. This reaction may be conveniently illustrated as follows:

, sn SR SR SR wherein X is ahalogen, Y is ammonium, an alkali metal tor alkaline earthmetal, and R is a hydrocarbon radical such asan alkyl, alkenyl, aryl or aralkyl group.

obtained by either of these methods.

acid, ayy-bis 3,5-dimethyl-2 heptenemercaptol The ammonium, alkali metal and alkaline earth metal salts Of-Ot,'y-bIS[hydl'OCaYbOIl substituted mercapto] butyric acids are conveniently produced by reacting the theoretical amount of about three molar equivalents of the corresponding ammonium, alkali metal or alkaline earth meta; hydrocarbon mercaptide' with one molar equivalent of an u,'ydihalobutyric acid. Although this ratio of reactants has been found most satisfactory, other ratios including an excess of either reactant may also be employed if desired.

The reaction may be conveniently achieved by contacting the mercaptide and a,' -dihalobutyric acid either in the presence or absence of an added solvent. In this regard, high yields of the desired product may be However, when the use of a solvent is desired inert organic solvents such as chloroform, carbon tetrachloride, toluene and lower alcohols may be employed with satisfactory results. In addition, water may be present in small amounts without adverse effect. Temperatures from about 0 C. to about C. are suitable for effecting the reaction. However, the lower reaction temperatures are ordinarily preferred'for effecting the reaction in the presence of a solvent while higher temperatures are employed when the reaction is carried out in the absence of a solvent.

The reaction is completed in a relatively short time, an hour being generally sufiicient under ordinary circumstances. When the reaction has been completed the correspondingammonium, alkali metal or alkaline earth metal salt of a,cy-bis[hydrocarbon substituted mercapto] butyric acid may be recovered by conventional methods .or converted directly to the free acid according to the succeeding .step. Examples of salts which may be prepared according to this process from the corresponding mercaptides are the ammonium, sodium, potassium, lithium, calcium and magnesium salts of a,'y-bis[methylmercapto] butyric acid, agy-bislethylmercapto] butyric acid, ,ecyy-biSlfiilYllIlfirClPtO] butyric acid, a,'y-bis[phenylmercapto] butyric acid, a,' -bis[benzylme rcapto] butyric acid, and the like.

The ammonium, alkali metal and alkaline earth metal salts of a,'y-bis[hydrocarbon substituted mercapto] butyric acids are converted to the corresponding u,'y-biS[hyd1'0- carbon substituted mercapto] butyric acids by acid hydrolysis. This reactionmay be conveniently accomplis'hedjby acidifying the reaction mixture from the previous step with a suitable acid, preferably a mineral acid such as phosphoric acid, hydrobromic acid, hydrochloric acid and the like. The product may then be isolated from the reaction mixture by conventional means such as extraction or.fractional distillation.

Illustrative oftheoverall process forming part of this invention is the production of u,'y-bis[methylmercapto] butyric acid by reacting a -dibromobutyric acid with sodium methylmercaptide to produce sodium-wy-bis- [methylmercapto] butyric acid which is hydrolyzed with hydrochloric acidto a,'y-bis-[methylmercapto] butyric acid. Examples of other similar compounds which may be produced according to this process are a,'y-bis[ethylmercapto] butyric acid, a, 'y-bis[propylmercapto] butyric mercapto] "butyriclacid, my-bisEallylmercapto] butyric V v butyric acid, 'rbisEZunethyl-l-ethyl-2 butenemercapto] butyric acid, fin DIS [3methyl-Z-ethyl-Z-pentenemercapto] butyric acid, u,'y-bis [phenylmercapto] butyric acid and ow -bis- .[benzylmercapto] butyric acid.

The a,' -dihal obutyric acids which are used as starting materials in this invention may be readily prepared by jhalogenating -butyrolactone with a phosphorous trihalide as is disclosed in U. S. Patent,No. 2,530,348. This reaction maybe achieved either with or Without the use ether, chloroform, benzene and the like.

esters,-like the acids, are water insoluble oils which may be purified by distillation under reduced pressure.

of an added solvent. However, some solvents which may be used if desired are chloroform, carbon tetrachloride,

benzene and hexane. The ayy-dihalobutyric acid formed according to this reaction may be used in the process of this invention as present in the reaction mixture or after its isolation therefrom by conventional methods. With regard to the present invention best results are obtained when eqy-dichlorobutyric acid or :,7-dib101110- butyric acid is used as the starting material.

Examples of ammonium, alkali metal and alkaline earth metal hydrocarbon mercaptides which may be used in this invention to produce the corresponding Ody-bis- [hydrocarbon substituted mercapto] butyric acids are sodium methylmercaptide, magnesium ethylmercaptide, potassium propylmercaptide, calcium butylmercaptide, sodium phenylmercaptide, potassium benzylmercaptide, ammonium methylmercaptide, potassium allylmercaptide, sodium 3,5-dimethyl-Z-heptenemercaptide, sodium 2-methyl- 1-ethy1-2-butenemercaptide, potassium 3-methyl-2-ethyl-2- pentenemercaptide, and the like. The sodium and potassium salts of the respective mercaptides are preferred for use in the described reaction.

7 'Also included within the purview of this invention are the esters of a,'y-bis[hydrocarbon substituted mercapto] butyric acids. In this regard, alkyl, aryl and aralkyl esters chloride, phthalyl chloride, phosphorous trichloride and the like. The reaction is readily achieved in a liquid 7 medium formed by using either an excess of the halogenating agent, when liquid, or an added inert organic solvent.- Temperatures of about 0-10 C. are ordinarily suitable for eitecting the reaction although higher tempe ratures may also be used. After the reaction has been completed the u,'y-bis[hydrocarbon substituted mercapto] butyryl. halide is recovered according to the conventionaliprocedures. Representative of the acyl halides priodricedinihis manner are a,' -bis[methylmercapto] butyryl chloride, a,'y-bis[ethylmercapto] butyryl bromide,

.a, y-bis[allylmercapto] butyryl chloride and the like.

: The,u,' bis [hydrocarbon substituted mercapto] butyryl halides produced as above may be conveniently esterified by reacting the acyl halide with anexcess of an alcohol corresponding to the ester desired. Thus, by reacting 04,7-

bis[methylmercapto] butyryl chloride with methanol the corresponding methyl ester is obtained. Examples of other esters which are prepared in a like manner are ethyl-a-y-bis[methylmercapto] butyrate, propyl-o -bis- [ethylmercapto] butyrate, butyl-u,'y-bis[propylmercapto] butyrate, methyl,a,' -bis[ethylmercapto] butyrate, benzyla,' -bis[methylmercapto] butyrate, methyl-a,y-bis[allylmercapto] butyrate, -methyl a,' -bis[phenylmercapto] butyrate and ethyl-u,'y-bis[benzylmercapto] butyrate.

In addition, lower alkyl esters may also be produced by reacting an ocyy-bis [hydrocarbon substituted mercapto] butyric acid with a diazoalkane, such as diazomethane or diazoethane, in a suitable dry inert solvent such as The resulting The orgy-bis [hydrocarbon substituted mercapto] butyric acids provided by this invention are useful in the production of -[3-(1,2-dithiacyclopentyl)] pentanoic acid, also called ot-lipoic acid. One such method for producing 5- V t3-(1,2-dithiacyclopentyl)] pentanoic acid, which process however, is not part of the present invention, being the invention of Holly, Wagner, Walton and Hoffman, Serial Examples of halogenating agents which may be used are thionyl chloride, oxalyl 4 No. 396,334 filed December 4, 1953, now Patent No.

2,809,978, comprises reacting an a,'y-bis[hydrocarbon substituted mercapto butyryl halide with a tert.-butyl ethyl malonic acid diester a-ethoxymagnesium derivative in an anhydrous solvent, adding water and acid to the reaction mixture to convert the resulting Grignard complex to a tert.-butyl-4,6-bis[hydrocarbon substituted mercapto]-2-carbethoxy-3-oxocaproate, treating said compound with p-toluenesulfonic acid to produce an ethyl- 4,6-bisi hydrocarbon substituted mercapto]-Ei-oxocaproate, reacting said compound with methyl fi-chloropropionate to form a methyl-6,8-bis[hydrocarbon substituted mercapto]-4--carbethoxy-5-oxocaprylate, deesterifying and decarboxylating said compound with a mixture of glacial acetic acid and hydrochloric acid to obtain 6,8-bislhydrocarbon substituted mercapto]-S-oxocaprylic acid, reducing said compound with sodium borohydride to the corresponding S-hydroxy caprylic acid which immediately forms a 6,8-bis[hydrocarbon substituted mercapto'l-S-hydroxy caprylic acid S-lactone, reacting said lactone in glacial acetic acid containing phosphorous and iodine to produce 6,8-bis[hydrocarbon substituted mercapto] caprylic acid and converting said compound to u-lipoic acid by dealkylation and reaction with iodine-potassium iodide. The a,v-bis[hydrocarbon substituted mercapto] butyric acids which may be used according to this synthesis' of a-lipoic acid are those in which the hydrocarbon substituent is an alkyl, alkenyl, aryl or aralkyl group such as the methyl, ethyl, allyl, benzyl and phenyl radicals.

According to a further embodiment of this invention compounds having the formula wherein R is a hydrocarbon radical such as "an alkyl,

aryl or aralkyl group and R is an alkyl group, may be produced according to an additional novel process. These compounds are also useful intermediates in the synthesis of 5-[3-(1,2-dithiacyclopentyl)] pentanoic acid, or alipoic acid.

Compounds having the described formula may-be conveniently produced by reacting an a-halo-y-butyrolactone with an ammonium, aikali metal or alkaline earth metal hydrocarbon mercaptide to produce an' a-hydrocarbon substituted mercapto-v-butyrolactone, reacting said com pound with an ammonium, alkali metal or alkaline earth metal alkyl mercaptide to produce the correspondingammonium, alkali metal or alkaline earth metal alkyl mercaptide addition product of the a-hydrocarbon substituted mercapto- -butyrolactone and heating said addition compound to produce the desired product. This process may be represented structurally as follows:

CHr-CH:

CHX R CH:C H2

UH-SR 0 i to-w-butyrolactones is.readily accomplished according to the first step of this process by reacting approximately.

one equivalent of an a-halo-y butyrolactone with about one-equivalent of anralka'li metal: or alkaline earthrmetal hydrocarbon mercaptide. This reaction may be conveniently achieved by contacting the'reactants in a suitable inert organic solvent such as the lower alcohols, hexane, benzene, toluene and inert chlorinated solvents such as chloroform and carbontetrachloride. The reaction is exothermic in nature and to prevent overheating the reactants are generally combined slowly and the mixture cooled by suitable means. In this connection, it is preferred to maintain a reaction temperature below 60 C. to prevent destruction of the reactants and the product. Usually an hour or so is sufiicient to complete the reaction after which the product may be recovered from the reaction mixture by conventional methods. One such method comprises evaporating the'solvent and purifying the product by extraction and fractional distillation.

a-Hydrocarbon substituted mercapto- -butyrolactones which are produced according to this process are u-alkyl, aryl and aralkyl mercapto-'y-butyrolactones such as ocmethylmercapto-v-butyrolactone, ot-ethylmercapto-y-butyrolactone, a-propylmercapt0-y-butyrolactone, a-phenylmercapto-' -butyrolactone and ot-bfillZYlHlfiICfltPtO-"y-blltyrolactone.

The a-halo-y-butyrolactones used as starting materials in this process may be prepared by the application of methods described in U. S. Patent No. 2,530,348 and the J. Am. Chem. Soc, 67, 2218 (1945). Specifically, a-chloro-v-butyrolactone and ot-bromo-v-butyrolactone are particularly suitable for this purpose.

Representative of the ammonium, alkali metal and alkaline earth metal hydrocarbon mercaptides which may be used as starting materials are the ammonium, sodium, potassium, lithium, calcium and magnesium salts of methylmercaptan, ethylmercaptan, butylmercaptan, phenylmercaptan and benzylrnercaptan.

In the second step of this process the (it-hydrocarbon substituted mercapto-y-butyrolactones are reacted with approximately one equivalent of a suitable ammonium, alkali metal or alkaline earth metal alkyl mercaptide to produce the corresponding ammonium, alkali metal or alkaline earth metal alkyl mercaptide addition product of the tar-hydrocarbon substituted mercaptoy-butyrolactone. This reaction is conveniently conducted in the presence of an inert non-hydroxylic solvent such as hexane, benzene, chloroform and the like. The addition product forms readily at ordinary temperatures and may be recovered from the reaction mixture by removing the solvent.

Examples of addition products which may be produced inthis manner are the sodium methylmercaptide addition product of a-methylmercapto-y-butyrolactone, the

potassium ethylmercaptide addition product of or-methylmercapto-v-butyrolactone, the sodium methylmercaptide addition product of u-benZylmercapto-y-butyrolactone and the like.

Ammonium, alkali metal and alkaline earth metal alkyl mercaptide addition products of a-alkylmercaptoy-butyrolactones may alsobe prepared according to a one step process, rather than according to the two step method previously described, by reacting directly about two equivalents of. a. suitable ammonium, alkali metal or alkaline earth metal alkyl mercaptide with one equivalent of an a-halo-ybuty rolactone.

According to this reaction the products produced have identical mercapto substituents, i. e., R=R, and are therefore. useful intermediates in preparing a -biSEalkylmercapto] butyric acids. The production of'these'addition products may be conveniently'achieved' according to the reaction conditions described above for the production of such compounds in two steps.

The ammonium, alkali metal and alkaline earth metal alkyl mercaptide addition products of why-drocarbon substituted mercaptoy-butyrolactones are converted to the corresponding a-hyclrocarbonsubstituted mercapto-v-alkyl mercapto butyric'acids accordingto. the next step ofthis process by heating the addition product at an elevated temperature. For this purpose; temperaturestof about ISO-200 C. are satisfactory although it is preferred to effect the reaction at about 170 C. At such temperatures the reaction goes to completion in about one hour. The product forms as an alkali metal or alkaline earth metal salt which may be conveniently recovered or hydrolyzed to the free acid without prior isolation by acidifying the reaction mixture to about pH 3 with a suitable mineral acid. Recovery of the mercapto substituted butyric acid is achieved according to conventional methods such as adding water to the-mixture and extracting the product with a water immiscible inertorganic solvent. By the application of this procedure a,'y-bis[alkylmercapto] butyric acids, such as the specific examples previously disclosed herein, and a-hydrocarbonsubstituted mercapto- 'yalkylmercapto butyric acids such as a-methylmercapto-y-ethylmercapto butyric acid, a-ethylmercapto-' -methylmercapto butyric acid, a-phenylmercapto- -ethylmercapto butyric acid, u-propylmercapto-yethylmercapto butyric acid and a-benzylmercaptwrmethylmercapto butyric acid may be produced from the appropriate butyrolactone addition product. Salts and esters of these and similar compounds may be produced by the methods previously described herein. Furthermore, these compounds may be used in the production of 5-[3-(1,2-dithiacyclopentyl)1 peutanoic acid by the procedure referred to prior hereto.

The following examples are included to illustrate specific embodiments of this invention.

EXAMPLE I Production. of a,'y-bis[methylmercapto] butyric acid To a solution of 77 gm. of sodiummcthoxide in 750 ml. of cold anhydrous methanol is added gm. of methylmercaptan. The mixture is stirred While*cooling by means of an ice bath. To the resulting solution of sodium methylmercaptide is added gm. of a,-y-dibromobutyric acid. The a -dibromobutyric acid is added dropwise over a period of 15 minutes during which the temperature of the reaction mixture rises to about 30-40 C. The reaction mixture containing the sodium salt of a,'y-bis[methylmercapto] butyric acid is concentrated to a small volume by evaporation on a waterbath under reduced pressure, 500 ml. of water is addedand the pH adjusted to 3 with hydrochloric acid. The ot,'ybis{methylmercapto] butyric acid separates. and is ex tracted with chloroform. The chloroform solution is extracted with aqueous sodium bicarbonate, and the'bicarbonate solution is acidified and extracted with chloroform. The chloroform solution is dried over magnesium sulfate and concentrated under reduced pressure to an oil. The or -bis[methylmercapto] butyric acid so obtained has a refractive index: vn =1.5276 aud a neutralization equivalent of 183 (theory 180);

The a, -dib1-omobutyric acid is prepared as follows: 280 gm. of 'y-butyrolactone and 10 ml. of phosphorous tribromide are combined and heated to 100 C. with stirring. Bromine is added to the'mixture for about 2.5 hours. During the first 1.5 hours the temperature is maintained at about -130 C. The-temperature is then lowered to 90 C. to prevent evolution of hydrogen bromide. After the bromine addition is complete the reaction mixture is heated at 90-95 C. for about 2 hours and then cooled. The solution contains org-dibromobutyric acid.

Production of methyl-a -bis[methylmercapto]. butyrate 13.29 gm. of a,'y-bis[methylmercapto] butyric acid is cooled in an ice-bath and 9.7 gm. of thiouyl chloride added thereto. The reaction mixture is allowed to stand overnight at ice-bath temperature and thenthe excess thionyl chloride is removed by distillation under dimin ished pressure. The residue, consisting essentially of a,'y-bis[methy1mercapto] butyryl chloride is cooled in an capto] butyrate.

7 ic bhthf 25 mil of methanol is added; After the evolution of gas ceases the mixture is concentrated under reduced pressure at 40 C. The residue, consisting of EXAMPLE ll 'Pi'ozluction of u,- -bis[ethylmercapto] butyric acid About 15.5 gm. of ethylmercaptanis added with stirring to a cold mixture of 14 gm. of potassium hydroxide in 200 ml. of ethanol. To the cold ethanolic solution of potassium ethylmercaptide is added 21 gm. of cam-Clibromobutyric acid with stirring over a period of 1 hour. The solvent is removed under diminished pressure leaving a residue consisting essentially of potassium-e,'y-bis lethylmercapto] butyrate. The residue is added to water, acidified to pH 3 and extracted with chloroform. By evaporating the chloroform solution under diminished pressure there is obtained a,'y-bis[ethylmercapto] butyric acid.

EXAMPLE III Production of nay-bis[butylmercapto] butyric acid A solution of sodium butylmercaptide is prepared by dissolving 27 gm. of sodium methoxide in 300 ml. of cold methanol and adding 45 gm. of butylmercaptan with cooling and stirring. To the cooled solution is added 39 gm. of u,'y-dibromobutyric acid and the mixture allowed to stand for several hours. After removing the solvent under diminished pressure 100 ml. of water is added to the residue of sodium-a,- bis[butylmercapto] butyrate. Concentrated hydrochloric acid is added to pH 3 and unreacted butylmercaptan removed by steam distillation. The residue containing [2,"Y-bl5 [butylmercapto] butyric acid is added to chloroform and extracted with aqueous sodium bicarbonate. The purified product is isolated by acidification of the aqueous solution, extraction with chloroform and removal of the solvent.

Production of ethyi-ouy-bislbutylmercnpto] biltyrmc About 0.1 mole of eta-bis[butylmercapto] butyric .acid is added slowly to 0.15 mole of thionyl chloride.

EXAMPLE TV Production of org-bis[phenylmercapto] butyric acid To 250 ml. of cold methanol is added 0.4 mole of sodium methylate and 0.4 mole of phenylmercaptan with stirring and-cooling. About 0.13 mole of a,'y-dibromobutyric acid is added to the cold solution of sodium phenylmercaptide and the mixture concentrated under reduced pressure to obtain sodium-aq-bis [phenylmer- The sodium salt is added to 100 ml. of water and the solution is steam distilled to remove excess phenylmercaptan and other impurities. The resi' due is added to water, acidified'aud the m,'y-bis[phenylmercapto] butyric acid extracted with chloroformand isolated by removing the solvent.

Production of methyl-wy-bis[phenylmercapto] butyrate j 0 .2 mole of a,'y-bis[phenylmercapto] butyric acid and 0.3 mole of thionyl chloride are reacted under anhydrous conditions at a slightly elevated temperature. Upon termination 'of the reaction the mixture is distilled at room temperature'under diminished pressure to remove excess thionyl chloride leaving a residue consisting of a,' -bis[phenylmercapto] butyryl chloride. The acid chloride is reacted with an excess of methanol to produce the methyl ester of a,'y-bis[phenylmercapto] butyric acid. The product is isolated and purified by conventional methods.

EXAMPLE V Production of nay-bis[benzylmercapto] butyric acid To a solution of 81 gm. of sodium methylate in 800 ml. of methanol is added 186 gm. of benzylmercaptan. About 123 gm. of a,'y-dibromobutyric acid is added dropwise to the mixture with cooling and stirring. The mixture is refluxed for about one hour, the methanol removed and the residue consisting of sodium-whis- [benzylmercapto] butyrate added to ice water. The aqueous solution is acidified with hydrochloric acid giving a -bisibenzylmercapto] butyric acid as an oil. The product is purified by dissolving it in ether, extracting with aqueous potassium bicarbonate, acidifying the aqueous solution with acid and extracting the product with ether. The purified a,'y-bislbenzylmercapto] butyric acid is recovered by removing the ether under reduced pressure.

Production of ethyl-u;y-bis[benzylmcrcapto] butyrate Approximately 0.2 mole of thionyl chloride is added to 0.15 mole of cooled a,'y-bis[benzylmercapto] butyric acid with stirring. After the initial vigorous reaction the mixture is allowed to warm to room temperature, stand for 1 hour and the excess thionyl chloride removed by evaporation under diminished pressure. The product is treated with ethanol and concentrated under diminished pressure. The residue is primarily ethyl-a -bis- [benzylmercapto] butyrate. It is purified by dissolving the product in chloroform, washing the chloroform solution with aqueous sodium bicarbonate and subsequently removing the solvent.

EXAMPLE VI Production of a-methylm ercapto-' -butyrolacet0ne A solution of 20.3 gm. of sodium methylmercaptide in 225 ml. of methanol is added to a cooled solution of 37.7 gm. of a-bromo-v-butyrolactone in 50 ml. of methanol. After standing at room temperature for about one hour the methanol from the reaction mixture is distilled off under diminished pressure and replaced with ml. of water. The impure a-methylmercapto'ybutyrolactone which separates out as an oil is extracted with chloroform. The resulting chloroform solution is washed with water and dried over magnesium sulfate. The chloroform is removed under diminished pressure leaving an oil which is distilled to give t-methylmercapto- -butyrolactone boiling at 64.0-66.5 C./ 0.1 mm., n =1.5040. The infrared spectrum discloses a lactone band at 5.68n and absorption in the 13-15 region which is indicative of the CS--C bond.

Production of the sodiummethylmercaptide addition product of ot-methylmercapto-y-butyrolactone Production of a,'y-bis[m'ethylmercapto] butyric acid from the sodium methylmercaptide addition product of mmezhylmercapto-y-butyrolactone The sodium methylmercaptide addition product of no methylmercapto-- butyrolactone prepared abovejis heated at about 165-170 C. for thirty minutes. After cooling the fused mixture to about 100 C. it is dissolved in 120 ml. of water and the solution adjusted to pH 3 with hydrochloric acid. The ot/y-biS [methylmercapto] butyric acid separates from solution and is extracted with chloroform. The chloroform solution is extracted with aqueous sodium'bicarbonate, the aqueous extract acidified with hydrochloric acid and extracted with chloroform.

The chloroform extract is washed with water and dried over magnesium sulfate. The chloroform is removed by evaporation under diminished pressure leaving substan tially pure a,'y-bis[methylmercapto] butyric acid as a heavy oil, B. P. 154-l58 C./0.15 mm., n =l.5267, neutralization equivalent=184 (theory 180). The infrared spectrum in carbon disulfide indicates a carboxylic acid with a C=O stretch at 5.85,u.

Production of methyl-aq-bisEntethylmercapto] butyrate An excess of diazornethane in ether is added to a cold solution of 1.3 gm. of u,y-bis[methylmercapto] butyric acidin .20 ml. of anhydrous ether. After standing at room temperature for minutes the ether is removed under reduced pressure. The resultingvoil is distilled under diminished pressure to give methyl-ayy-bis [methylmercapto] butyrate, "B. P. 7274 C./0.13 mm., n =1.5097.

EXAMPLE VII Production of the potassium ethylmercaptide addition product of a-methylmercaptoy-butyrolactone A solution of 0.1 mole of a-methylmercaptoy-butyrol- ..actone,prepated as inExample VI, in 30 ml. of-toluene gisadded with stirring to a suspension of 0.12 mole of po- .,t,assiu rn ethylmercaptide in 5.0 ml.. of toluene. The mixtureis stirred for several hours at about 20-40 vC. and the;toluene removedunder reduced pressure to obtain the potassium ethylmercaptide addition product of a-methylmercapto-v-butyrolactone.

Productionof a-methylmercapto-v-ethylmercapto butyric acid The potassium ethylmercaptide addition product of amethylmercaptoy-butyrolactone prepared above is heated at 150180 C. for 45 minutes, cooled and dissolved in water. The aqueous solution of potassium-a-methylmercapto-v-ethylmercapto butyrate is acidified to pH 3 with concentrated hydrochloric acid and extracted with chloroform. The chloroform solution is extracted with aqueous sodium bicarbonate, the aqueous extract is acidified and finally extracted with ether. The a-methylmercapto-v-ethylmercapto butyric acid is isolated by removing the ether and is purified by distillation under diminished pressure.

EXAMPLE VIII Production of a-propylmercapto-v-butyrolactone To a solution of 0.3 mole of potassium propylmercaptide in 250 ml. of ethanol is added 0.3 mole of a-bromo- 'y-butyrolactone. The reaction proceeds quickly to give a mixture containing a-propylmercapto-'y-butyrolactone. The product is isolated by removing the solvent, pouring the residue into water, extracting with chloroform and evaporating off the chloroform. It is further purified by fractional distillation.

Production of the sodium ethylmercaptide addition product of a-propylmercapto-y-butyrolactone The a-propylmercapto-w-butyrolactone produced according to the method described above is reacted with an equivalent amount of potassium ethylmercaptide in 70 ml. of toluene. The mixture is stirred overnight at room temperature and the sodium ethylmercaptide addition product of a-propylmercaptow-butyrolactone recovered by distilling off the solvent.

aerate Production of a-propylmercapto-v-ethylmercapto -butyric acid The sodium ethylmercaptide addition product of apropylmercapto-y-butyrolactone from above is fused at about 170 C. for about 30 minutes, cooled and added to .250 ml. of water. The aqueous solution of sodium ,a-propylmercapto-'y-ethylmercapto butyrate is acidified and extracted with ether. By removing the ether there is obtained a-propylmercapto-y-ethylmercapto butyric acid.

EXAMPLE IX Production of u-benzylmercapto-'y-butyrolactone Production of the sodium .methylmercaptide addition product of a-benzylmercapto-y-butyroluctone To a stirred solution of 0.4 mole of arbenzylmercapto- -butyrolactone in 40 ml. of toluene is added a suspension of 0,5 mole ofsodium methylmercaptide in ,150 ml.

of benzene. The mixture is maintained at 20-40 C. for one hour and the benzene removed under reduced pressure to give the sodium methylmercaptide addition product of a-benzylmercapto-v-butyrolactone.

Production of a-benzylmercapto-'y-methylmercapto butyric acid Approximately 0.1 mole of the sodium methylmercap- .tide addition productof a-benzylmercapto butyrolactone is heated to -180" C. for two hours, cooled and added to water. 'The aqueous solution of sodium a-benzylmercapto- -methylmercapto butyrate is acidified, .extractedwith ether and the ether removed to give a-benzylmercapto-'y-methylmercapto butyric acid.

EXAMPLE X Production of a;y-bis(allylmercapto) butyric acid About 1.5 mole of allyl bromide is added dropwise to a stirred refluxing solution of 1.5 moles of thiourea in 500 ml. of methanol over a period of fifteen minutes, and refluxing is then continued for an additional thirty minutes. A solution of three moles of potassium hydroxide in methanol is next added rapidly and the solution refluxed for another twenty minutes.

The solution of potassium allylmercaptide thus prepared is cooled and 0.5 mole of a,'y-dibromobutyric acid is added. The mixture is allowed to stand at room temperature overnight, and then concentrated under reduced pressure. The residue is diluted with water and acidified With concentrated HCl. The desired product is isolated from the acidic solution by extraction with chloroform and subsequent removal of the solvent under reduced pressure. The product had the following physical constants: Neut. equiv. 247 (calc. 232); mol. Wt. (ebulliometric) 241:4 (calc. 232); sulfur 25.68% (calc. 27.60%).

Production of a,'y-bis(allylmercapto) butyryl chloride A benzene solution containing 13 g. of ct,' -bis(allylmercapto) butyric acid is cooled in an ice bath and 5 ml. of thionyl chloride added. The mixture is stirred with cooling for one hour, the excess thionyl chloride removed under reduced pressure and a,'y-bis(allylmercap- 11 to) butyryl chloride purified by distillation: B.-P. 130- 137 C./1-2 mm.; n =1;5456.

Production of methyl-ayy-biflallylmercapto) butyrate Twenty ml. of cold methanol is added to 4.0 g. of a,'y-bis(allylmercapto) butyryl chloride and the mixture allowed to stand. The excess alcohol is removed under reduced pressure and the residue distilled to give methylmm.; n =1.528O.

What is claimed is:

1. A compound selected from the group consisting of compounds having the structure where R is selected from the group consisting of lower alkyl, lower alkenyl, phenyl and benzyl radicals, R is a lower alkyl radical and Y represents ammonium, alkali metals and alkaline earth metals.

2. A compound having the structure wherein R is a lower alkyl radical and Y is an alkali metal.

3. The process for the production of a compound having the formula which comprises intimately contacting in an inert solvent medium approximately one equivalent of an 06-11310-7- butyrolactone with approximately two equivalents of a compound having the structure YSR, in each occurrence R representing a lower alkyl radical and Y representing a member of the group consisting of ammonium, alkali metals and alkaline earth metals.

4. The process for the production of a compound having theforrnula which comprises intimately contacting in an inert solvent medium approximately one equivalent of an a-halo-vbutyrolactone with approximately one equivalent of a compound having the structure YSR to produce a compound having the formula CHz-CHz CH-SR OC ll 0 and intimately contacting in an inert solvent medium said compound with approximately one equivalent of a compound having the structure YSR,'where in each occurrence R is selected from the group consisting of lower alkyl, lower alkenyl, phenyl and benzyl radicals, R is a lower alkyl radical and Y represents a member of the group consisting of ammonium, alkali metals and alkaline earth metals.

5. A compound having the structure 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF COMPOUNDS HAVING THE STRUCTURE 